Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome : A MAGNIMS multicentre study

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research has been supported by a programme grant (14-358e) from the Dutch MS Research Foundation (Voorschoten, The Netherlands). The study in London was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.Background: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain. Objectives: The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis. Methods: We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3-6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010). Results: In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T (p = 0.005). For patients, this was 4.18 and 4.40, respectively (p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters. Conclusion: Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training

Liever inleiden dan afwachten bij aterme zwangerschapshypertensie en milde preeclampsie: HYPITAT-studie

OBJECTIVE: To investigate what would benefit women with mild full-term pregnancy-related hypertension most: induction of labour or expectant monitoring, from the perspective of clinical effectiveness, maternal quality of life, and costs. DESIGN: Randomised clinical trial. Trial registration number ISRCTN08132825. METHODS: We undertook a multicentre randomised controlled trial in 38 hospitals in the Netherlands between October 2005 and March 2008. We enrolled patients with a singleton pregnancy in cephalic presentation at 36-41 weeks' gestation, who had gestational hypertension or mild preeclampsia. Participants were randomly allocated to receive either induction of labour or expectant monitoring. The primary outcome was a composite measure of poor maternal outcome, defined as maternal mortality, maternal morbidity (eclampsia, 'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome, pulmonary oedema, thrombo-embolic disease and abruptio placentae), progression to severe hypertension or proteinuria, and major postpartum haemorrhage. Secondary outcomes were mode of delivery, neonatal outcome, maternal quality of life and costs. Analysis was by intention to treat. RESULTS: A total of 756 patients were allocated to receive induction of labour (n = 377 patients) or expectant monitoring (n = 379). No cases of maternal or neonatal death or eclampsia were recorded. Development of poor maternal outcome was significantly lower in the induction of labour group (117 women) than the expectant monitoring group (166 women) (31% versus 44%; relative risk 0.71 (95% CI: 0.59-0.86); p < 0.001). The caesarean section rate was lower among women in the induction of labour group (n = 54) compared to women in the expectant monitoring group (n = 72) (14% versus 19%; relative risk 0.75 (95% CI: 0.55-1.04)< p = 0.085). Neonatal outcomes and quality of life were comparable between both groups. Induction of labour is a cost saving strategy (difference euro 831). CONCLUSION: For women with full-term gestational hypertension and pre-eclampsia, induction of labour is associated with improved maternal outcome and lower costs, without the additional risk of a caesarean section being necessary

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Comparing long-term results of PASAT and SDMT scores in relation to neuropsychological testing in multiple sclerosis

Background and objectives: The Symbol Digit Modalities Test (SDMT) shows advantages over the Paced Auditory Serial Addition Test (PASAT) as a cognitive test in patients with multiple sclerosis (MS). To determine which of these tests is most valid and reliable over time as an indicator of the cognitive state of MS patients, long-term test results of both tests were compared in relation to scores of the Brief Repeatable Battery of Neuropsychological tests (BRBN). Methods: For 485 MS patients visiting the VU University Medical Center Amsterdam for different research projects, a total number of 1078 visits with BRBN (including PASAT and SDMT) was planned. Observed and model-based correlations were used to calculate the construct validity of the SDMT and PASAT 3 seconds test (PASAT3) by comparing correlations with the BRBN-sumscore. The test-retest reliability of each test was also computed. Results: For the construct validity, higher correlations were found between SDMT and BRBN compared to PASAT3 and BRBN, especially for the model-based correlations at baseline. The reliability of the measurements was good for all instruments, with the highest coefficients for the SDMT. Conclusion: As a single assessment tool for cognition in MS, the SDMT is more valid and reliable compared to PASAT3. © The Author(s) 2013

Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women

BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. METHODS: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m2. Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m2increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women

Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements

PURPOSE: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. METHODS: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. RESULTS: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8–94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). CONCLUSION: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: HOVON-84: EudraCT: 2006–005,174-42, retrospectively registered 01–08-2008. HOVON-130: EudraCT: 2014–002,654-39, registered 26–01-2015 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05498-7

Successful Treatment of MYC rearrangement Positive Large B Cell Lymphoma Patients with R-CHOP21 Plus Lenalidomide: Results of a Multicenter Phase II HOVON Trial

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Randomized Trial of a Lifestyle Program in Obese Infertile Women

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An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial)

Objective To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term. Design An economic analysis alongside the Hypertension and Preeclampsia Intervention Trial At Term (HYPITAT). Setting Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. Population Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring. Methods A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon. Main outcome measures One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease. Results The average costs of induction of labour (n = 377) were (sic)7077 versus (sic)7908 for expectant monitoring (n = 379), with an average difference of -(sic)831 (95% CI -(sic)1561 to -(sic)144). This 11% difference predominantly originated from the antepartum period: per woman costs were (sic)1259 for induction versus (sic)2700 for expectant monitoring. During delivery, more costs were generated following induction ((sic)2190) compared with expectant monitoring ((sic)1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs. Conclusion In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial

Background Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. Methods We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation. with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome-maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 ml, blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. Findings 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Interpretation Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. Funding ZonMw